Ensuring adequate food availability to an increasing world population constitutes one of the biggest challenges faced by humankind. Scientific and technological advances in food production during the last century enabled agriculture to cope with the concomitant increase in food demand. For example, cereal yields have more than doubled from a global average of 1.5 metric tons per hectare in the 1960s up to 3.2 metric tons per hectare in 2018. This was made possible by the work in different research fields such as agronomy, engineering, and plant sciences, showing that an inter and multidisciplinary approach is indispensable for significant progress. This manuscript is aimed at generating reflexion and analysis about the challenges that agriculture faces at present to satisfy projected food demands, which implies a further doubling of food production by 2050, according to the latest estimates. Relevant issues related to food production (climate change, pollution of water and soils by pesticides and fertilizers, loss of germplasm and biodiversity) are discussed and potential solutions to achieve food security in quantity and quality are reviewed, mainly from the plant breeding and crop-production perspectives, always associated with environmental health preservation and improvement. A broad transdisciplinary effort is needed to increase the impact of science and technology to provide more people with healthier and safer food, produced in a sustainable way. Nonetheless, science and technology alone will not succeed to meet those challenges. Education and knowledge transfer strategies are needed to guarantee responsible production and consumption everywhere, therefore allowing the benefits of scientific and technological progress reach the world population. Simultaneously, adequate action by regulatory authorities and governments concerted at international level, with thorough application of the Precautionary Principle, and aiming at environmental and social justice are imperatively required to meet the challenge and achieve the goal.