Tobacco dependence is a chronic, relapsing condition driven by rapid nicotine reinforcement, conditioned cues, and withdrawal that erodes sleep, mood, and cardiometabolic health. Tobacco Cessation translates strong evidence into practical steps that fit real clinics—primary care, psychiatry, inpatient units, and telehealth. We start with why quit attempts fail: underestimated withdrawal, unmanaged stress spikes, and cue-laden routines (waking, commuting, caffeine, alcohol, screens). Assessment maps dependence (time to first cigarette/vape, cigarettes per day, nocturnal use), co-occurring conditions (depression, anxiety, bipolar disorder, psychosis), and medications that interact with quit pharmacotherapy. First-line pharmacology is combination therapy: long-acting controller plus short-acting reliever. We show how to size combination NRT to actual intake, escalate dosing early, and switch when adherence or side effects block progress. For varenicline, we cover flexible starts (standard, gradual “reduce-to-quit,” inpatient), nausea mitigation, and pairing with behavioral supports; for bupropion SR, we discuss insomnia prevention, seizure risk, and when it helps with comorbid low mood or weight concerns. Behavioral work is brief and focused: cue restructuring, urge surfing, “if-then” plans tied to high-risk times, and digital prompts for micro-wins. Equity is built in: language access, cost-sensitive formularies, and pharmacy synchronization; for people with serious mental illness, we coordinate antipsychotics/mood stabilizers with quit meds and monitor for dose adjustments as smoking status changes. Hospitalizations and pregnancies are leveraged as windows of motivation with tailored protocols. Follow-up cadence matters: weekly early, then step-downs; we track withdrawal, sleep, and function—not just abstinence—so partial progress is still reinforced. Finally, we normalize relapse as learning: update trigger maps, redeploy meds, and move again. With this approach, Tobacco Cessation, the community and methods of a tobacco cessation conference, and core tools like combination NRT convert more first tries into durable quits.