Differences in mode of action between biologic agents could explain why one agent is more efficacious than another in the treatment of recalcitrant and erythrodermic flares of chronic plaque psoriasis. Here, we present our experience using a case series of three patients with chronic plaque psoriasis who showed consistent and similar responses to three different biologic agents. All three patients who were refractory to efalizumab developed erythrodermic flares 2-12 weeks after a direct switch to etanercept. Switching from efalizumab to etanercept could provoke paradoxical flaring of psoriasis, which might be prevented by transitioning to systemic agents. The erythrodermic flares in all three patients responded dramatically to infliximab with marked and maintained improvements in Psoriasis Area and Severity Index scores.