Controlled environment agriculture (CEA) is a growing industry for the production of leafy vegetables and fresh produce in general. Moreover, CEA is a potentially desirable alternative production system, as well as a risk management solution for the food safety challenges within the fresh produce industry. Here, we will focus on hydroponic leafy vegetable production (including lettuce, spinach, microgreens, and herbs), which can be categorized into six types: (1) nutrient film technique (NFT), (2) deep water raft culture (DWC), (3) flood and drain, (4) continuous drip systems, (5) the wick method, and (6) aeroponics. The first five are the most commonly used in the production of leafy vegetables. Each of these systems may confer different risks and advantages in the production of leafy vegetables. This review aims to (i) address the differences in current hydroponic system designs with respect to human pathogen internalization risk, and (ii) identify the preventive control points for reducing risks related to pathogen contamination in leafy greens and related fresh produce products.