Monoclonal gammopathy with undetermined significance (MGUS) is the most common plasma cell disorder, MGUS is an asymptomatic premalignant disorder, which is markedly underdiagnosed in the general population. The risk frequency of progression to multiple myeloma or a closely related plasma cell disorder was developed at a rate of 1.5% per year, indicating that the condition is not entirely benign. The cumulative probability of progression is 10% at 10 years, 21% at 20 years, and 26% at 25 years. As compared with control populations, the progression rate of MGUS into multiple myeloma, Waldenstr m's macroglobulinemia, AL amyloidosis and lymphoma were increased by 25, 46, 8.4 and 2.4 times respectively. Numerous reports suggest an association of MGUS with a wide variety of other malignant and nonmalignant diseases. The determining highest risk factors of progression, delaying or preventing the progression of MGUS, targeting at the highest risk of progression and improving overall quality of life, all of them are the current hot topics to be explored and summarized in this review.