Over the past 100 years, psoriasis therapy was fortunately explored by coincidence and recommendation that greatly depended on narrations and anecdotes. However, nowadays psoriasis therapy tales are still valid as suggestions for trials and studies, but target therapies are always provided based on evidence and international guidelines. Diagnosing and evaluating psoriasis is mainly clinical. There are several clinical manifestations of psoriasis. Psoriatic lesion needs to be carefully differentiated from atypical presentations. Although psoriasis cure has not yet been discovered, the systemic and regional approach of the disease must depend on the latest and updated evidence-based practice. This review will highlight a wide range of clinical and therapeutic aspects regarding the diagnosis and latest drugs developments to help dermatologists in confirming and managing psoriasis. This review is a recommended evidence-based data that was formulated using PubMed and Google scholar electronic database and NICE.org website for recent clinical guidelines. Skin biopsy is essential in confirming the diagnosis, as psoriatic lesion needs to be carefully differentiated from atypical presentations. The management of psoriasis requires extensive patient education, screening for comorbidities, and monitoring the needed therapy depending on the changes.