In recent times it has become increasingly clear that releases of trace gases from human activity have a potential for causing change in the upper atmosphere. However, our knowledge of systematic changes and trends in the temperature of the mesosphere and lower thermosphere is relatively limited compared to the Earth's lower atmosphere, and not much effort has been made to synthesize these results so far. In this article, a comprehensive review of long-term trends in the temperature of the region from 50 to 100 km is made on the basis of the available up-to-date understanding of measurements and model calculations. An objective evaluation of the available data sets is attempted, and important uncertainly factors are discussed. Some natural variability factors, which are likely to play a role in modulating temperature trends, are also briefly touched upon. There are a growing number of experimental results centered on, or consistent with, zero temperature trend in the mesopause region (80–100 km). The most reliable data sets show no significant trend but an uncertainty of at least 2 K/decade. On the other hand, a majority of studies indicate negative trends in the lower and middle mesosphere with an amplitude of a few degrees (2–3 K) per decade. In tropical latitudes the cooling trend increases in the upper mesosphere. The most recent general circulation models indicate increased cooling closer to both poles in the middle mesosphere and a decrease in cooling toward the summer pole in the upper mesosphere. Quantitatively, the simulated cooling trend in the middle mesosphere produced only by CO2 increase is usually below the observed level. However, including other greenhouse gases and taking into account a “thermal shrinking” of the upper atmosphere result in a cooling of a few degrees per decade. This is close to the lower limit of the observed nonzero trends. In the mesopause region, recent model simulations produce trends, usually below 1 K/decade, that appear to be consistent with most observations in this region.