Alternative crops, combined with modern farming methods, are integral parts of the new agricultural model and dominant priorities of agricultural policy. The new conditions created in the internal and global markets of agricultural products indicate significant opportunities for growing alternative crops and for the introduction of modern farming practices and processing. The present study aims to assess the factors that determine the landholder’s decision to uptake an alternative crop. Primary data were gathered through a quantative survey (in-depth interviews) with landholders in two remote and less-favored prefectures of Northeastern Greece, and were analysed through a logistic regression model. The results indicate that the most significant determinants for adopting an alternative crop involve the scientific support to farmers, the development of product demand in the market, the creation of agricultural cooperatives, the development of promotional campaigns for the alternative products, the education and knowledge regarding alternative crops, and the landholder’s satisfaction with income. On the contrary, negative factors to their decision refer to exports development, product subsidies, landholder’s age, membership to a cooperative in its current form, and satisfaction with pesticides prices. Despite the dominance of conventional agriculture models and varieties, the new favorable investment conditions can spur the promotion of alternative crops.