Globalization, climate change, malnutrition and HIV-AIDS are posing unprecedented challenges to rural families. Smallholder farmers in southern African are partnering with researchers and change agents to innovate in response to this rapidly changing environment. Experiences will be reported from a Client, Agroecological Niche and Development Oriented (CANDO) approach developed in Malawi. Smallholders investigated the long-term consequences of informal irrigation systems, crop diversification and intensified resource use of riverine habitat, wetlands and upland fields. Agro-ecological analysis was linked to farmer participatory research to improve testing of livelihood options and understanding of sustainability trajectories. Transects were carried out and on-farm trials initiated collaboratively, to investigate soil nutrient dynamics in relationships to land use. Project challenges included donor mandates and scientist attitudes that privileged specific commodities, ‘improved’ varieties and government agricultural recommendations.  This was addressed in part by shifting the scale of research from field to region, and integration of ecologically-based understanding to community management strategies.  Integration of organic and inorganic nutrient sources proved highly relevant. Results from soil characterization validated the ability of smallholder farmers to manage soil quality in wetland areas. The complexity of gender and power relations was illustrated by the investments in soil fertility made by women farmers, which were one-third higher than men farmers. Overall, the project documented the value of, and farmer demand for, more knowledge-based training. To achieve relevance, participatory approaches require careful attention to engaging with farmers and bringing the best biological understanding to avoid the default of proscriptive agricultural recommendations.