This overview and network meta-analysis of Cochrane reviews evaluates the efficacy and safety of pharmacological interventions for smoking cessation. The primary outcomes are long-term abstinence (six months or longer) and the incidence of serious adverse events. The overview includes 12 Cochrane reviews covering 267 studies with over 101,804 participants. **Key Findings:** - **Nicotine Replacement Therapy (NRT):** Both NRT and bupropion were superior to placebo, with odds ratios (OR) of 1.84 and 1.82, respectively. - **Varenicline:** Increased the odds of quitting compared to placebo (OR 2.88). - **Bupropion:** Equal efficacy to NRT (OR 0.99) and superior to single forms of NRT (OR 1.59). - **Cytisine:** Positive findings without significant adverse events or serious adverse events (SAEs). - **Nortriptyline:** Increased the chances of quitting (RR 2.03). - **Clonidine:** Helped people quit but caused side effects. - **Other Treatments:** Did not demonstrate a benefit compared to placebo. **Conclusions:** - NRT, bupropion, varenicline, and cytisine improve the chances of quitting with a low risk of harms. - Combination NRT is as effective as varenicline and more effective than single types of NRT. - Cytisine has potential as a safe, effective, and affordable treatment. - Nortriptyline improves the chances of quitting with minimal evidence of harmful events. - Further research is needed on the safety of varenicline and the potential of cytisine. - Additional research on NRT versus placebo is unlikely to change the understanding of treatment efficacy.This overview and network meta-analysis of Cochrane reviews evaluates the efficacy and safety of pharmacological interventions for smoking cessation. The primary outcomes are long-term abstinence (six months or longer) and the incidence of serious adverse events. The overview includes 12 Cochrane reviews covering 267 studies with over 101,804 participants. **Key Findings:** - **Nicotine Replacement Therapy (NRT):** Both NRT and bupropion were superior to placebo, with odds ratios (OR) of 1.84 and 1.82, respectively. - **Varenicline:** Increased the odds of quitting compared to placebo (OR 2.88). - **Bupropion:** Equal efficacy to NRT (OR 0.99) and superior to single forms of NRT (OR 1.59). - **Cytisine:** Positive findings without significant adverse events or serious adverse events (SAEs). - **Nortriptyline:** Increased the chances of quitting (RR 2.03). - **Clonidine:** Helped people quit but caused side effects. - **Other Treatments:** Did not demonstrate a benefit compared to placebo. **Conclusions:** - NRT, bupropion, varenicline, and cytisine improve the chances of quitting with a low risk of harms. - Combination NRT is as effective as varenicline and more effective than single types of NRT. - Cytisine has potential as a safe, effective, and affordable treatment. - Nortriptyline improves the chances of quitting with minimal evidence of harmful events. - Further research is needed on the safety of varenicline and the potential of cytisine. - Additional research on NRT versus placebo is unlikely to change the understanding of treatment efficacy.