Cocoa cultivation began with the Olmecs, who were the first humans to consume chocolate as a drink in equatorial Mexico between 1500 and 400 BC. Over the centuries, commercial cocoa cultivation and trade have developed from the Mayans, Aztecs, and through Meso-America under the influence of the Spanish explorers. In 1822, cocoa was first introduced to São Tomé and Príncipe in Africa from where it spread as a plantation crop, with West Africa becoming the major centre of global production. The cultivation of selected hybrid varieties particularly have led to pest and diseases becoming major production limiting factors. This chapter evaluates crop protection techniques developed over the years, and highlights their contribution to yields, production costs, impact on farmers, and the cocoa value chain and ecosystems. We discussed the need to re-evaluate the imbalance of power in the global value chain, the colonial trading systems, and the required investments for integrated disease and pest management systems. The prospects of using modern biotechnological tools to improve cocoa, and how these approaches can reduce the negative impacts of current protection measures on the ecology and production systems are highlighted. Key recommendations have been made for all stakeholders in the cocoa industry to ensure future sustainability.