Recently, the discovery of active microbial life in deep-sea sediments has triggered a rapid development of the field known as the “deep biosphere.” Geomicrobiological investigations in lacustrine basins have also shown a substantial microbial impact on lake sediments similar to that described for the marine record. Although only 30 % of the lake sites drilled by the International Continental Drilling Program (ICDP) have included microbial investigations, these lakes cover a relatively wide range of salinities (from 0.15 to 33.8 %), pH (from 6.0 to 9.8) and environmental conditions (from very arid to humid subtropical conditions). Here, we analyze results of very recent ICDP lake sites including subsurface biosphere research from southern Patagonia (Laguna Potrok Aike) to the Levantine area (Dead Sea) as well as the East Anatolian high plateau (Lake Van) and Macedonia (Lake Ohrid). These various settings allow the examination of the impact of contrasting environments on microbial activity and their subsequent role during early diagenesis. Furthermore, they permit the identification of biosignatures of former microbial activity recorded in the sediments as well as investigating the impact of microbes in biogeochemical cycles. One of the general outcomes of these preliminary investigations is data to support the hypothesis that microbes react to climatically driven environmental changes that have a direct impact on their subsurface distribution and diversity. This is clear at conspicuous levels associated with well-known climatic periods such as the Medieval Climatic Anomaly or the Little Ice Age. Although more research is needed, this relationship between prevailing microbial assemblages and different climatic settings appears to dominate the lacustrine sites studied until to date.