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Intensification of smallholder agriculture in sub-Saharan Africa is necessary to address rural poverty and natural resource degradation. Integrated soil fertility management (ISFM) is a means to enhance crop productivity while maximizing the agronomic efficiency (AE) of applied inputs, and can thus contribute to sustainable intensification. ISFM consists of a set of best practices, preferably used in combination, including the use of appropriate germplasm, the appropriate use of fertilizer and of organic resources, and good agronomic practices. The large variability in soil fertility conditions within smallholder farms is also recognized within ISFM, including soils with constraints beyond those addressed by fertilizer and organic inputs. The variable biophysical environments that characterize smallholder farming systems have profound effects on crop productivity and AE, and targeted application of agro-inputs and management practices is necessary to enhance AE. Further, management decisions depend on the farmer's resource endowments and production objectives. In this paper we discuss the “local adaptation” component of ISFM and how this can be conceptualized within an ISFM framework, backstopped by analysis of AE at plot and farm level. At plot level, a set of four constraints to maximum AE is discussed in relation to “local adaptation”: soil acidity, secondary nutrient and micronutrient (SMN) deficiencies, physical constraints, and drought stress. In each of these cases, examples are presented whereby amendments and/or practices addressing these have a significantly positive impact on fertilizer AE, including mechanistic principles …