The elaboration and implementation of the National/Regional Innovation Strategy for Smart Specialisation (RIS 3) has become an important component of the cohesion policy for 2014-2020 programming period and an ex-ante condition for the EU countries in accessing structural funds. In its aspirations for the European integration (the Republic of Moldova signed the RM-EU Association Agreement in 2014) and opting for the penetration into the single community market, the Republic of Moldova faces challenges generated by the necessity to ensure the country's economic competitiveness and sustainable growth. This ambitious goal can be achieved through a broad process of innovation, reconsidering the R&D system, changing the paradigm of economic development. An effective solution to this is RIS3. The opportunity to develop RIS3 for the Republic of Moldova has been mentioned in several national and European documents. This process was initiated recently in Moldova (2016) with support of the Joint Research Centre of the EC, being at the initial stage of its development. The paper highlights the importance of the Smart Specialisation Strategy (S3) and the impact this process can have on the economic restructuring and growth, emphasizes the peculiarities and advantages of S3, analyzes the economic and research potential of the Republic of Moldova, characterizes the current situation of the S3 process in the country, the challenges it faces and the actions to be followed in order to develop the Smart Specialisation Strategy in Moldova.