Previous studies have reported inconclusive results regarding the effects of Orthodox religious fasting (OF) on common cardiovascular risk factors, including arterial hypertension and diabetes. Contrariwise, an optimal effect on dyslipidemia has been demonstrated and significant reductions in total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) concentrations, in Orthodox populations without comorbidities, have been consistently reported. This favorable effect on lipid homeostasis is probably facilitated by a broad lifestyle modification related to OF, extended beyond dietary habits. However, several clinical issues require further clarification by future trials including the efficacy and safety of OF in specific groups of patients with dyslipidemia, mainly those with cardiovascular disease and diabetes, the effects of OF on high-density lipoprotein-cholesterol (HDL-C), the dietary limitations of specific vitamins and minerals during fasting, as well as the optimal duration of this dietary intervention. The present article aims to discuss, whether there is a strong enough theoretical background, to currently support the implementation of OF as a medical nutrition therapy for dyslipidemia in the daily clinical setting, with a discourse on available evidence and future research agenda.