Potato (Solanum tuberosum L.) is an important crop for food security and cash income for smallholder farmers in Uganda. However, the national mean potato yield has been in decline to less than 5 Mg ha-1 in 2016. Low productivity of potato might be associated with poor and diverse adoption of innovative crop management practices. Smallholder farmers in Uganda commonly use seed potato tubers from the informal sector, especially by seed recycling over several generations. Therefore, seed tubers are highly degenerated with viruses and other diseases, resulting in poor yield and quality of the produce. Over one cycle of multiplication, the degeneration management by positive seed selection was found to be efficient in reducing virus diseases compared with the farmers’ method of selection. The aim of this thesis was to provide novel information regarding understanding positive seed selection by investigating it across multiple cycles of multiplication with an interdisciplinary approach.