A number of theoretical fatigue frameworks have been developed by nurse scientists with the intention of guiding research, practice, and education in fatigue. However, there is a significant gap between theory development and research utilization of fatigue frameworks in clinical and intervention trials. The purpose of this report is to assess an example of an inductive fatigue framework and a deductive symptom management model: The Integrated Fatigue Model (IFM) and the revised University of California, San Francisco, Symptom Management Model (UCSF-SMM), to investigate their potential to guide future nursing research projects on fatigue. The IFM is a fatigue-specific comprehensive framework of 14 biological and psychosocial patterns that influence signs and symptoms of fatigue and trigger six fatigue dimensions. The developers emphasized that patterns could be interrelated and influence the dimensionality of fatigue. The UCSF-SMM is a multidimensional symptom management model embedded within the three nursing domains: person, environment, and health and illness. The model places symptom perceptions, symptom management strategies, and outcomes within these nursing domains to be the key components of a highly complex symptom management process. The IFM is an important development in the understanding and conceptualization of fatigue in cancer and in HIV/AIDS. However, it does not reach the level of integration of the UCSF-SMM in taking fatigue research a significant step forward by integrating symptom impact, symptom management, and symptom outcomes. Both models have significant weaknesses because of their complexity.