Psoriasis is a chronic inflammatory disease that affects not only the skin but also systemic health, including cardiovascular risk. Recent research has highlighted that treatment choice in psoriasis can significantly influence the likelihood of major cardiovascular events. In a new study, methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) emerged as the safest systemic therapies with respect to cardiovascular outcomes. The study evaluated the incidence of myocardial infarction, stroke, and cardiovascular mortality in patients receiving various systemic treatments for psoriasis. Patients treated with MTX and TNFi had a noticeably lower risk of these adverse events compared to those on other systemic agents such as cyclosporine, acitretin, or newer biologics targeting other pathways. The findings suggest that these therapies provide cardioprotective effects, likely due to their potent anti-inflammatory properties, which help mitigate the systemic inflammation that contributes to atherosclerosis. Methotrexate, long used as a first-line systemic therapy, demonstrated not only dermatologic efficacy but also measurable cardiovascular benefit, reinforcing its role in patients with psoriasis who have elevated cardiovascular risk factors. TNFi therapies, widely used in moderate-to-severe cases and in psoriatic arthritis, also showed substantial reductions in cardiovascular events, positioning them as preferred options for patients with dual dermatologic and cardiovascular concerns. Importantly, the study highlighted that cardiovascular safety is not uniform across all systemic psoriasis treatments. Some therapies showed neutral or uncertain effects, emphasizing the need for clinicians to consider cardiovascular profiles alongside efficacy when prescribing systemic medications. The investigators recommend that dermatologists collaborate with cardiologists in managing patients with psoriasis and comorbid cardiovascular risk factors. Additionally, they call for continued research into the mechanisms by which systemic anti-inflammatory therapies reduce cardiovascular risk and long-term outcomes associated with prolonged use.