Fatigue and cognitive complaints commonly occur during adjuvant chemotherapy treatment of breast cancer. Fatigue is also associated with radiation therapy, and can occur with surgery alone. Both of these symptoms may persist beyond the initial treatment of breast cancer and they have taken on greater prominence with the growing number of breast cancer survivors. These symptoms are most troublesome when patients try to resume their pre-illness activities (e.g., work, household responsibilities) and find that they are limited. Recovery may take months to years, but in some women these symptoms persist indefinitely and can be very distressing. In this chapter we review what is known about the etiology and biology of these two common symptoms, discuss potential interventions, and describe future research challenges.