Lactic acid bacteria (LAB) play a critical role in food, agricultural, and clinical applications. The fast growing characteristics of LAB and their metabolic activity have been the key in most applications including food production, agricultural industry, and probiotics. However, the biochemical and biophysical environments have significant effect on the growth and metabolic activity of LAB. While the biochemical conditions are most likely established, controlling and optimizing of biochemical conditions have many limitations and challenges. In addition to selecting the right strain, desirable metabolic processes required optimizing and controlling the available nutrients including sugars, peptides, free amino acids, minerals, and vitamins in addition to buffering agents. Thus, much of research was conducted to understand the impact of available nutrients on the growth and metabolic activities of LAB. However, only a few nutritional parameters could be controlled at a time while holding other parameters constant. The nutritional parameters may also interact with each other resulting in faulty results. Characteristics of LAB such as fastidiousness in their nutritional requirements, ability to produce acid and antimicrobial compounds, and variations in the nutritional requirements among strains have added additional limitations and challenges in this regard. Thus, chemically defined media (CDM) were suggested to deal with different limitations and challenges. However, due to differences in growth conditions, results obtained in CDM may face some obstacles when it comes to industrial applications. Thus, this paper aimed to review the recent data in regard to the role of the nutritional requirements of LAB in optimizing and controlling metabolic activities and to discuss the associated limitations and challenges.