We are entering a new era in the management of patients with multiple sclerosis (MS). The first oral treatment (fingolimod) has now gained US FDA approval, addressing an unmet need for patients with MS who wish to avoid parenteral administration. A second agent (cladribine) is currently being considered for approval. With the arrival of these oral agents, a key question is where they may fit into the existing MS treatment algorithm. This article aims to help answer this question by analyzing the trial data for the new oral therapies, as well as for existing MS treatments, by applying practical clinical experience, and through consideration of our increased understanding of how to define treatment success in MS. This article also provides a speculative look at what the treatment algorithm may look like in 5 years, with the availability of new data, greater experience and, potentially, other novel agents.