Treatment options for patients newly diagnosed with multiple sclerosis (MS) are expanding with the continuous development and approval of new disease-modifying therapies (DMTs). The optimal initial treatment strategy, however, remains unclear. The 2 main treatment paradigms currently employed are the escalation (ESC) approach and the early highly effective treatment (EHT) approach. The ESC approach consists of starting a lower- or moderate-efficacy DMT, which offers a potentially safer approach, while the EHT approach favors higher-efficacy treatment early in the disease course, despite a potential increase in risk. Randomized clinical trials aiming to directly compare these approaches in newly diagnosed MS patients are currently underway.