Bortezomib with or without dexamethasone has been reported to be very effective and well tolerated in the treatment of AL amyloidosis. Commonly reported adverse effects are fatigue, nausea, vomiting, diarrhea, constipation, postural hypotension from autonomic neuropathy, peripheral neuropathy, thrombocytopenia and anemia. Dyspnea has been rarely reported as an adverse effect of bortezomib therapy in AL amyloidosis. We are reporting three case reports of patients suffering from AL amyloidodis, who had new onset acute dyspnea secondary to bortezomib treatment that required drug discontinuation. There might be some correlation between the AL amyloidosis disease and bortezomib associated dyspnea, but the pathophysiology is poorly understood.