Sugarcane is a strategic cash crop having a deep impact on social and governmental issues on many people around the globe. Rapid climatic change and intensification as mono-culture cropping of sugarcane, world trade, and extensive use of chemical products have amplified the risk of regular recurrence of disease/pest outbreaks and incursions. Any sugarcane variety development program must consider adaptation to biotic stressors. Understanding the causes of biotic stress resistance implies knowledge of sugarcane taxonomy. Various wild species are still being studied for their ability to withstand biotic stresses. The major issues involving the most widely spread diseases, such as ratoon stunting, rust, and smut, as well as its history and explanation, have been thoroughly examined. Plants respond to pathogen infection by upregulating the expression of glucanases, chitinases, thaumatins, peptidase inhibitors, defensins, catalases, and glycoproteins, among other proteins. Pathogen-induced proteins are engaged in plant defense either directly or indirectly, resulting in pathogen death or generating additional plant defense responses. Effective management of pests/diseases in sugarcane agroecosystems is based on integrated crop managing scenarios. This chapter focuses on agricultural practices and their influence on pests/disease, biological, chemical control, transgenic varieties, and the use of GIS in sugarcane integrated pest management.