Disclosed herein are genetic markers related to the efficacy and/or safety of thiazolidinedione therapy identified by a physiogenomic methodology that correlates the genetic markers with a physiological response. The genetic markers described herein were not previously associated with the efficacy and/or safety of thiazolidinedione therapy. The markers related to safety are those associated with the important side effects of BMI increase and development of edema. In one embodiment, markers related to efficacy of thiazolidinedione therapy are associated with glycosylated hemoglobin. Method of assessing an individual for markers associated with the safety and/or efficacy of thiazolidinedione therapy are described.