Prognostic factors in myeloma are not only important for allowing comparisons to be made between therapeutic protocols but they also provide us with an insight into the pathophysiology of the disease and important mechanisms which result in disease progression. Prognostic factors in myeloma relate to the inherent proliferative capacity of the malignant clone, tumor bulk, renal function and other factors which reflect tumor host and host tumor interactions. The highly significant effect of the labelling index (LI) suggests that the clonogenic cell is ontologically very close to the malignant plasma cell on which the labelling index is derived. The explanation for the important role of the beta 2-microglobulin (beta 2M) level over and above its reflection of renal function is as yet unclear. Other factors involved in prognosis such as serum cytokines (IL-2 and IL-6) and soluble IL-6 receptor levels reflect host tumor interactions. An understanding of these interactions may allow us to control the disease and prevent escape from plateau phase by biological means. This may become a viable alternative to high dose aggressive chemotherapy which up till now appears unable to eradicate the malignant clone.