Tobacco smoking is the world's leading cause of premature death and disability. Global targets to reduce premature deaths by 25% by 2025 will require a substantial increase in the number of smokers making a quit attempt, and a significant improvement in the success rates of those attempts in low, middle and high income countries. In many countries the only place where the majority of smokers can access support to quit is primary care. There is strong evidence of cost-effective interventions in primary care yet many opportunities to put these into practice are missed. This paper revises the approach proposed by the International Primary Care Respiratory Group published in 2008 in this journal to reflect important new evidence and the global variation in primary-care experience and knowledge of smoking cessation. Specific for primary care, that advocates for a holistic, bio-psycho-social approach to most problems, the starting point is to approach tobacco dependence as an eminently treatable condition. We offer a hierarchy of interventions depending on time and available resources. We present an equitable approach to behavioural and drug interventions. This includes an update to the evidence on behaviour change, gender difference, comparative information on numbers needed to treat, drug safety and availability of drugs, including the relatively cheap drug cytisine, and a summary of new approaches such as harm reduction. This paper also extends the guidance on special populations such as people with long-term conditions including tuberculosis, human immunodeficiency virus, cardiovascular disease and respiratory disease, pregnant women, children and adolescents, and people with serious mental illness. We use expert clinical opinion where the research evidence is insufficient or inconclusive. The paper describes trends in the use of waterpipes and cannabis smoking and offers guidance to primary-care clinicians on what to do faced with uncertain evidence. Throughout, it recognises that clinical decisions should be tailored to the individual's circumstances and attitudes and be influenced by the availability and affordability of drugs and specialist services. Finally it argues that the role of the International Primary Care Respiratory Group is to improve the confidence as well as the competence of primary care and, therefore, makes recommendations about clinical education and evaluation. We also advocate for an update to the WHO Model List of Essential Medicines to optimise each primary-care intervention. This International Primary Care Respiratory Group statement has been endorsed by the Member Organisations of World Organization of Family Doctors Europe.