Mild cognitive impairment (MCI), an intermediate stage between normalcy and dementia, is characterized by fewer symptoms and less functional decline than dementia with less established biological disease processes and is an attractive target for both symptomatic and disease progression therapies. It is always desirable to treat symptoms or slow disease at a stage where the individual is still largely functional. Therapeutic studies in MCI have either been symptomatic, usually of shorter duration or of longer multiyear terms to demonstrate whether disease progression is delayed. Symptomatic agents tested to date include donepezil, SGS-742, and Piracetam. No symptomatic drug study has demonstrated clinically convincing differences between placebo and the study medication. Disease progression trials in MCI investigations of 2 to 4 year durations have included donepezil, vitamin E, rivastigmine, galantamine and rofecoxib. None have demonstrated convincing effects in delaying longer term disease progression or conversion to dementia. Problems that may have undermined these trials; i) disease heterogeneity, ii) slow early progression of the disease, and iii) insensitive cognitive and functional instruments. Future MCI studies may benefit from the use of biomarkers such as apolipoprotein E (APOE4), cerebrospinal fluid amyloid-beta1-42 and Tau levels and PIB positivity on brain PET scans as well as more sensitive neuropsychological test measures may also more accurately reflect clinical changes related to drug effects.