Inorganic fertilizers will play a role in government programs, but whether or not a single policy is valuable for all farmers depends upon the net gain for the farmers. The research here seeks to demonstrate how to answer the question “Is fertilizer profitable in Zambia for maize and cotton in the smallholder sector?” This study identifies the key components determining profitability and then sets up a framework to evaluate the probability of farmers to obtain profitable results with fertilizer use on maize and cotton. Several cases are selected and the results are evaluated. Private profitability for the farmer at market prices is discussed, leaving social profitability to other researchers. A simple method for farmers and extensionists to use to assess a fertilizer investment is given, to assist in more site specific analysis, given prices and environment.