For decades, concern has been mounting that individuals with systemic lupus erythematosus (SLE) have increased susceptibility to cancer. Recent data confirm that certain cancers, particularly hematologic, occur more frequently in SLE than in the general population. Numerous pathogenic mechanisms are possible, but hypotheses remain largely speculative. In particular, data are inadequate on how cancer risk in SLE may be related to medication exposures. To evaluate the impact of medication exposures on cancer risk in SLE, cooperative efforts of Systemic Lupus International Collaborating Clinics and Canadian Network for Improved Outcomes in Systemic Lupus are currently in progress. This should provide much-needed insight into the pathogenesis of the association between cancer and SLE.