The paper examines the role of SME sector in Moldova’s economy and its likely implications in the RD processes. Several key features of the relationship between knowledge economy, RD and SMEs are emphasized, and also their effect on regional and local communities. Then, a summary of RD particular features in Moldova is presented. The role of SME sector, examined in terms of its performance by ownership and activity types, as a whole and by main firms’ categories (micro-, small, and medium-sized) is analyzed. Small enterprises have been considered as the most adequate solution for promoting RD in general case. National-level analysis is completed by regional insight into the sector as a whole. Finally, some critical aspects of SMEs’ role in RD in Moldova are discussed.