A variety of conditions result in lower extremity edema, such as deep vein thrombosis, cellulitis, venous stasis insufficiency, and congestive heart failure (CHF). A case study is presented to illustrate the dynamics of the lymphatic system, the pathology of CHF, the importance of obtaining a pretreatment differential diagnosis, and how to implement a safe treatment plan. The patient was a 69-year-old overweight woman with bilateral lower extremity lymphedema of almost equal volume (~9,100 mL) of >2 months' duration. She had 11 draining wounds and a reported history of chronic obstructive pulmonary disease (COPD) but no cardiac dysfunction. Treatment consisted of 6 sessions of manual lymph drainage (MLD), remedial exercises, and compression wrapping and weekly volumetric measurements over a period of 3 weeks. A 4-L decrease in lower extremity edema volume was noted, but fatigue and shortness of breath increased markedly. Treatment was discontinued and the patient was referred back to her physician for cardiac evaluation and treatment. The literature suggests patients, as well as health care professionals, do not always distinguish CHF symptoms from COPD. Proper assessment, monitoring, and lymphedema treatment adjustments are paramount to providing safe care for patients with signs and symptoms of COPD and suspected CHF. More research to elucidate best practice approaches in patients with lymphedema and concurrent CHF/COPD before the start of MLD treatment is warranted.