Formation of a seroma most frequently occurs after mastectomy and axillary surgery. Prolonged drainage is troublesome as it increases the risk for infection and can significantly delay adjuvant therapy. Seroma has been defined as serous fluid collection under the skin flaps or in the axillary dead space following mastectomy and/or axillary dissection. Because the true etiology of a seroma is unknown, a multifactorial-causation hypothesis has been accepted. Surgical factors include technique, extent of dissection and the surgical devices used for dissection. Obliteration of dead space with various flap fixation techniques, use of sclerosants, fibrin glue and sealants, octreotide, and pressure garments have been attempted with conflicting results and none have been consistent. Early movement of the shoulder during the postoperative period may increase the formation of seroma, although delayed physiotherapy decreases the formation of seroma. A detailed analysis of the use of drains showed that use of single or multiple drains, early or late removal, and drains with or without suction are not significantly different for the incidence of seroma. Although there is evidence for reduced seroma formation after early drain removal, very early removal within 24 hours seems to increase formation of seroma. No patient or tumor factors seem to affect seroma formation except body mass index and body weight. Consensus is lacking among studies/trials with different groups producing conflicting evidence. Besides a few established factors such as body mass index, the use of electrocautery for dissection, early drain removal, low vacuum drains, obliteration of dead space, and delayed shoulder physiotherapy, most of the hypothesized causes have not been demonstrated consistently. Thus, seroma remains a threat to both the patient and surgeon. Recurrent transcutaneous aspiration remains the only successful management.