Despite an increasingly recognized relationship between depression and smoking, little is known about the degree to which treatment studies for depression consider the impact of smoking on outcomes. The aim of this study is to examine the extent to which smoking is considered in current antidepressant treatment research. We conducted a MEDLINE search of recent randomized clinical trials of pharmacotherapy for depression published between 1 January and 31 December 2007, and a search of current pharmacological intervention studies for depression using www.ClinicalTrials.gov. Only 5% of the 107 pharmacological trials for depression published in 2007 reported the smoking status of their samples. Two studies (1.9%) controlled for smoking in the analyses and no studies analyzed outcomes by smoking status. Excluding the eight studies of combined treatment for depression and nicotine dependence, no other study on www.ClinicalTrials.gov (total n = 920) reported an intention to analyze outcomes by smoking status. Emerging data link smoking and depression, however, little attention has been directed toward the effects of smoking on antidepressant treatment outcomes. Conducting research to understand how nicotine and smoking affect responsiveness to antidepressants would advance our understanding of the neurobiology of depression and the development of new and targeted treatments.