While there are various avenues for performance improvement in college American football (AF), there is no comprehensive evaluation of the collective array of resources around performance, physical conditioning, and injury and training/game characteristics to guide future research and inform practitioners. Accordingly, the aim of the present review was to provide a current examination of these areas in college AF. Recent studies show that there is a wide range of body compositions and strength characteristics between players, which appear to be influenced by playing position, level of play, training history/programming, and time of season. Collectively, game demands may require a combination of upper- and lower-body strength and power production, rapid acceleration (positive and negative), change of direction, high running speed, high-intensity and repetitive collisions, and muscle-strength endurance. These may be affected by the timing of and between-plays and/or coaching style. AF players appear to possess limited nutrition and hydration practices, which may be disadvantageous to performance. AF injuries appear due to a multitude of factors-strength, movement quality, and previous injury-while there is also potential for extrinsic factors such as playing surface type, travel, time of season, playing position, and training load. Future proof-of-concept studies are required to determine the quantification of game demands with regard to game style, type of opposition, and key performance indicators. Moreover, more research is required to understand the efficacy of recovery and nutrition interventions. Finally, the assessment of the relationship between external/internal-load constructs and injury risk is warranted.