This paper investigates the adoption of Open Innovation in the bio-pharmaceutical industry, studying through which organisational modes it is put into practice and how these modes are interwoven with the different phases of drug discovery and development process. Two rounds of interviews with industry experts were carried out to develop a model describing the adoption of Open Innovation by bio-pharmaceutical companies. This framework was then applied to an extensive and longitudinal empirical basis, which includes data about the adoption of Open Innovation by the top 20 worldwide industry players, in the time period 2000–2007. The paper provides a thorough discussion of how bio-pharmaceutical firms have used different organisational modes (i.e. licensing agreements, non-equity alliance, purchase and supply of technical and scientific services) to enter into relationship with different types of partners (i.e. large pharmaceutical companies, product biotech firms, platform biotech firms and universities) with the aim to acquire (Inbound Open Innovation) or commercially exploit (Outbound Open Innovation) technologies and knowledge. The implications of the study for Open Innovation research and possible avenues for future investigation are discussed at length in the paper.