On paper, who would have thought the best laughs this midseason come from a drug addict in rehab and a woman who may be dying from cancer? Showtime knows what makes us laugh -- while NBC's new Wednesday half-hour flunks the test.

NURSE JACKIE (Season 4 starts April 8; Sunday at 9 p.m. ET, Showtime)

There is no show on television that skates the fine line between comedy and outright tragedy as brilliantly as Nurse Jackie. Just as we are mesmerized by the despicable behavior of nearly everyone on Mad Men, we don't avert our gaze from the train wreck that is Edie Falco's drug-addicted ER nurse Jackie. We may squirm, but we recognize her.

The counterpoint to Falco's brittle brilliance is provided by Merritt Wever, who may be one of the funniest, quirkiest and most nuanced actresses working anywhere today. Weaver, who plays Nurse Zoey, is simply incandescent. When she's not in a scene, I miss her. I love every gutsy choice she makes, as if she does not care how weird she's playing it. I usually hate when an actor's performance is called brave -- we're not talking firemen or soldiers here, we're talking acting -- but Weaver has found someplace to dump all her self-consciousness, and she wobbles out on the high wire in every episode.

In fact, all the inhabitants do this season, as All Saints Hospital is taken over by a conglomerate that elevates the slick Dr. Miguel Cruz (Bobby Cannavale) over administrator Gloria Akalitus (Anna Deavere Smith), who's forced back to the nursing floor of the ER so she can collect her full pension. Even some nifty guest stars -- Rosie Perez, Aida Turturro, Joel Grey, Cannavale's real-life son Jake, and the New York Knicks' Carmelo Anthony -- know how to center their off-center characters. There's not a stiff in the bunch, and hats off to casting execs Julie Tucker and Ross Meyerson, who have an eye and an ear for the truth. Particular kudos to Laura Silverman's turn as Jackie's counselor at rehab, who's as much a heavyweight as Falco in the scenes they share as she fights for Jackie to take responsibility for her life.

In the first episode, Jackie finally admits she needs help, but her 28 days in rehab are not going to go any more smoothly than her life on the outside. Her husband, her kids, her lover, her friends, her colleagues and her addiction all present roadblocks she may or may not be able to overcome. Falco effortlessly blots out memories of Carmela Soprano to inhabit a character so flawed, she's perfect.

THE BIG C (Season 3 starts April 8; Sunday at 9:30 p.m. ET, Showtime)

Last year's season finale of The Big C ended with Cathy (Laura Linney) finishing a race and seeing the ghosts of her dead loved ones, including her husband (Oliver Platt) cheering her on at the finish line. Of course, we saw that he suffered a heart attack at a company Christmas party, so we too believe he has passed on. Linney's collapse -- she seemed to pancake in on herself as she fell -- was so devastating that I replayed it a number of times to try and figure out how an actress can be that good. Clearly, Showtime has that market cornered with both Falco and Linney starring in the network's most offbeat comedies, and I applaud Showtime for going dark with this block.

Trying to arrest her late-stage cancer, Cathy's been taking part in a trial helmed by Alan Alda. (Who wouldn't want their doctor to be Alda?) This third season opens with results that will color how Cathy and the rest of her family approach the time she has left. Though The Big C tackles an uncomfortable subject in a way, this show is a lot easier on the wince factor than Nurse Jackie. The Big C cast, save for Cathy's son (a most natural Gabriel Basso), strains toward quirkiness rather than embracing the skew like Nurse Jackie-land. A little of Cathy's brother (John Benjamin Hickey) and house guest Andrea (Gabourey Sidibe) goes a long way. And I'm actually happy to say goodbye to an irritating turn by Cynthia Nixon as Cathy's best friend and brother's lover.

BEST FRIENDS FOREVER (Series premieres April 4; Wednesday at 8:30 p.m. ET, NBC)

I could do without the feminine "to wax or not to wax" jokes, and the rhythms don't really improve in this comedy about the single BF (Lennon Parham) who rallies around the other (Jessica St. Clair) whose marriage has just gone south.

But for me, the truest sitcom test is, A) After 22 minutes, do I care enough about the characters to come back?, B) Did I laugh and care about the characters?, C) Was the show so genuinely funny, all I can remember is that I laughed my butt off, so it doesn't matter as much about the characters.

Best Friends Forever doesn't pass the A/B/C test, but D) It has its moments (like the Braveheart scene). There just aren't enough of them to elevate this to keeper status.