Psoriasis is a T helper (Th)17/Th1-mediated autoimmune disease affecting the skin and joints. So far, distinct traditional oral compounds and modern biologics have been approved in most countries for the treatment of patients with moderate to severe psoriasis or psoriatic arthritis. Yet, the anti-psoriatic therapeutic spectrum is to be extended by a number of novel targeted therapies including biologics and modern oral compounds. The next set of anti-psoriatic biologics targets mainly Th17-associated cytokines such as IL-17 or IL-23. In contrast, modern oral anti-psoriatics, such as dimethyl fumarate (DMF), apremilast or Janus kinase (JAK) inhibitors interfere with intracellular proteins and affect signaling pathways. Here we summarize the current systemic therapies for psoriasis and their immunological mechanism. The recent advances in psoriasis therapy will help treat our patients efficiently and complete our understanding of disease pathogenesis.