Over the course of the last decade advances in the understanding the pathogenesis of psoriasis have resulted in the development of many novel, safe and effective biologics. However, a significant proportion of patients respond inadequately to biologics--defined by failing to respond initially (lack of efficacy) or secondary failure--with diminishing response over time (loss of efficacy). Over the past years insights into molecular and genetic profiles have allowed to better define psoriasis phenotypes and to explain these therapeutic failures. Here we will illustrate these advances, describe the novel therapeutics on the horizon and review the current view of psoriasis as a systemic disease associated with co-morbidities and its important implications for the management of psoriatic patients.