Not much is known about the role of skin pH in skin pathophysiology, in particular in psoriasis. However, there is compelling evidence that the epidermal pH can influence the skin homeostasis and affect the skin barrier by changing the activity of cutaneous enzymes and through the modulation of skin inflammation and microbial colonization. This includes the activation of secretory phospholipase A and interaction with the peroxisome proliferators-activated receptor and retinoid pathways. In addition, pH in skin affects the activity of aquaporins and this controls the hydration of the epidermis. Changes in skin homeostasis, differentiation, barrier defects, and inflammation play a crucial role in the pathogenesis of psoriasis. There is evidence that skin pH can affect all of these important factors. However, more studies are needed to examine objectively and precisely the pH in the various skin layers in psoriatic lesional and non-lesional skin and compare it to normal skin. This additional know-how is essential to understand the role of skin pH in psoriasis with ultimately great potential of manipulations of skin pH for topical approaches in the management of psoriasis.