The TNF-alpha antagonists infliximab, etanercept and adalimumab have similar efficacies in clinical trials in the rheumatic diseases, and this efficacy may be related primarily to their neutralizing free TNF-alpha. Thus, a reasonable question for clinicians is whether patients who have failed one TNF-alpha antagonist could reasonably be given a trial with another such agent, or whether this is simply a waste of time and money. Several published studies have addressed this important practical issue and are reviewed in this paper. Data from the Stockholm TNF-alpha follow-up registry "STURE" that address this issue are described in detail. The overall conclusion appears to be that such switches of biologicals can be effective. Nonetheless, further attention should be paid to the details of various clinical scenarios in which this question can arise and the methods by which comparisons are made of treatment effects occurring during sequential therapies.