The thiazolidinediones pioglitazone and rosiglitazone are effective in improving glycemic control among patients with type 2 diabetes mellitus, but recent evidence has suggested a possible increased risk of cardiovascular events associated with these drugs. Two articles in this issue provide additional data to assess these risks. Lincoff and colleagues Article analyzed pooled data from 19 randomized clinical trials of pioglitazone and found that compared with patients receiving placebo or a comparator drug, patients who received pioglitazone had a significantly lower risk of death, myocardial infarction, or stroke but experienced an increased risk of serious heart failure. Singh and colleagues Article analyzed pooled data from 4 randomized trials of rosiglitazone and found that patients receiving rosiglitazone for at least 12 months had a significantly increased risk of myocardial infarction and heart failure compared with patients receiving a placebo or comparator drug. In an editorial, Solomon and Winkelmayer Article discuss these findings in the context of measures to improve drug safety.