DESAFIO means “challenge” in both Portuguese and Spanish. The guiding concept of our proposal is to make a contribution towards tackling what is arguably one of the major challenges facing Brazil and Latin American countries in the 21st century: eradicating structural social inequality in the access to essential water and sanitation services. The overarching objective of our proposal is assessing existing experiences and developing new strategies that bring about sustainable, appropriate, and innovative socio-technical solutions to foster economic and social development through social transformation in vulnerable communities, particularly with reference to access to safe water supply and sanitation in urban, peri-urban, and rural areas of South America, with a particular emphasis on Brazil. These strategies will be developed through research and networking that actively engages beneficiary communities, practitioners, local authorities, and other relevant actors in their planning, design, assessment, implementation, monitoring, validation, and diffusion. Our transdisciplinary approach is predicated on a close interaction with non-academic actors in the production and validation of knowledge, among other things to underpin policy and behavioural transformations. We have selected a number of case studies that will cover a range of situations and characteristics, from informal settlements in the urban periphery of world megacities (Rio de Janeiro, Brazil) and in peri-urban areas of provincial capitals (Cali, Colombia), favelas located in the heart of booming mid-range urban centres (Recife, Brazil), to small rural villages (Mondomo, Colombia) and communities in semi-arid areas (Ceará and Minas Gerais, Brazil and Santa Fe, Argentina). We will endeavour to draw lessons and develop recommendations that are applicable to other socio-cultural and economic contexts across the developing world.