A subset of patients with moderate-to-severe psoriasis show long-term remission after drug withdrawal lasting well beyond several half-life times of the drug, particularly following effective treatment with modern biologics such as interleukin-23 inhibitors. Furthermore, evidence suggests that the development of comorbidities, including psoriatic arthritis, a key comorbidity causing irreversible damage, can be prevented or delayed in a subgroup of patients with psoriasis receiving these therapies. This implies that psoriasis treatments may alter the underlying disease mechanisms in some individuals, extending beyond their direct pharmacological effects. However, this concept of disease modification remains controversial, as predicting the natural clinical course of an individual patient with psoriasis is challenging, and typically, no permanent clinically detectable changes occur in psoriatic skin inflammation. This article aims to provide an overview of the current evidence on disease modification in psoriasis and discusses clinical and molecular markers that could be used to predict or monitor disease modification in psoriasis.