One-year simple NPK trials were conducted in 22 locations in four regions of Colombia to determine the response of cassava (Manihot esculenta Crantz) to N, P and K and to relate this response to the available P and K contents of the soil, as well as to the N, P, and K concentrations in youngest fully expanded leaf (YFEL) blades sampled at 3–5 months after planting. It was found that cassava responded mainly to P applications in the low-P soils of the Eastern Plains and of Cauca Department, to K applications only in the Eastern Plains and to N applications principally in the sandy, low-OM soils of the Atlantic Coast. By relating the relative response to P and K to the available P and exchangeable K content of the soil, respectively, critical levels of 4 mg P/kg and 0.17 me K/100 g (both extracted with Bray II) were determined. Similarly, critical levels of 5.6% N, 0.41% P and 1.42% K were determined in YFEL-blades. A long-term fertilizer trial with 35 treatments was conducted for 8 consecutive years in the highly acid low-fertility soil at CIAT-Quilichao, to determine the effect of cassava production and fertilization on soil fertility. Although the first year response was mainly to P and N, already in the second year K became the most limiting nutrient and the importance of K fertilization increased over the years. This trial, and similar long-term fertility trials conducted in Colombia and in various parts of Asia, have all shown the importance of adequate annual applications of K for maintaining high yields of continuously grown cassava.