Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.