Ten million people will have died yearly from tobacco-related diseases worldwide by the 2030s. Smoking remains the largest preventable cause of premature death and disability in many countries. Fortunately, over the past 15-20 years, substantial progress has been made in research on anti-smoking therapy. The movement towards evidence based medicine has resulted in a greatly increased emphasis on the need for good research. For example, advice in primary care, more intensive interventions, nicotine replacement therapy, behavior therapy, and some other interventions have been investigated in randomized controlled trials. Likewise developments such as meta-analytic techniques and clinical guidelines raise hopes that progress will continue. However, various methodological problems still remain. This paper discusses these topics and others, including study design, control groups, participants, sample size, abstinence issues, types of therapists and their experience, intensity of interventions and statistical issues.