A wide range of support is available to help smokers to quit and to aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications with (1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and (2) 24 alternative products: cytisine (novel outside Central and Eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective serotonin reuptake inhibitors, supplements (e.g. St John's wort), silver acetate, Nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOIs), opioid antagonists, nicotinic acetylcholine receptor (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate (NMDA) receptors, dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors and the weight management drug lorcaserin. Six 'ESCUSE' criteria-relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients) and relative ease of use-are used. Many of these products are in the early stages of clinical trials; however, cytisine looks most promising in having established efficacy and safety with low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered.