Biomedical research collaborations are to be contextualized in the larger global health agenda which also opens up new information pathways, expands research networks, and brings additional resources. A qualitative inquiry was employed to understand the perceived benefits and challenges of research collaborations by biomedical scientists from India (Global South [GS] country) and the Global North (GN). In-depth interviews were conducted with 47 biomedical scientists from India and 06 from the GN. The data was analyzed using the grounded theory approach. Complementarity of skills and resources, access to funds, improved quality of work, an opportunity to conduct multi-centric studies, development of collaborative networks, better and larger number of publications, mutual learning, opportunity to work with credible researchers, address common interests, leverage interpersonal and trusted relationships and larger societal good were some of the critical factors for eagerness of participants in joint scientific endeavors. However, the challenging aspects of dissent and disagreements were the power imbalance between the collaborators, the development of a trust deficit, and local administrative issues. The challenges reported in the current publication, also echoed in several previous publications can be surmounted and negotiated amicably when the rules of the game, law of the land, sharing of the credits, and interest of the collaborating parties are addressed and agreed up in a fair and just manner before the start of the collaboration. Overall biomedical partnerships are complex collaborations with its challenges, the processes are dynamic and outcomes are emergent. This requires constant and proactive evolution of the preparation, implementation and sustainability of the collaborative efforts be it national or international.