The physical presentation of psoriasis and its impact on health-related quality of life (HRQoL) varies greatly between patients as well as over the course of the disease. A number of instruments have been developed for evaluating disease severity and its impact on HRQoL, the best known being the Psoriasis Area and Severity Index (PASI). HRQoL is most commonly evaluated using the Dermatology Life Quality Index (DLQI) and/or the Short-Form-36 Health Survey (SF-36). The exact correlation between the reduction of skin symptoms upon therapy and changes of HRQoL is not known. Since improvement of HRQoL is being established as an independent goal of psoriasis therapy, a better understanding of the relationship between skin symptoms and HRQoL during treatment will likely influence not only disease concepts but also physicians treatment decisions. Based on a selective review of the literature, this paper focuses on recent insight obtained from clinical trials with infliximab on the correlation between skin clearance and changes of HRQoL in psoriasis and compares these findings with results from studies with other biologics. Together these data indicate that despite the lack of a direct correlation between absolute PASI and DLQI values, significant reductions of PASI are likely to correlate with significant improvements of HRQoL. There is also evidence, that large improvements of HRQoL as currently discussed as treatment goals in psoriasis are primarily achieved in patients with an at least 75% reduction of their PASI.