Navigation of the Mekong River is restricted by numerous natural obstructions. These include complete barriers to vessel movement such as Khone Falls in Lao PDR. In other areas, rapids, shoals and sharp bends may block all traffic or limit passage to smaller vessels – important locations include lengths of the Mekong River in Yunnan (Lancang River) and extending southward along the Myanmar-Lao PDR border and into northern Thailand, and along the southern portion of Lao PDR.

River navigation is also constrained by low discharge in the dry season and in some areas, riverbank erosion and channel sedimentation. In many areas, safe navigation suffers from a lack of recent hydrographic data and navigation aids in combination with aging vessels involved in transport on the river, weak navigation skills and limited port facilities and operation.

Improvements are planned for navigation along the Mekong River and major tributaries. Important improvements to navigation that are being considered include large-scale removal of obstructions on the Lancang-Mekong River from Yunnan to northern Thailand, dredging of the Great Lake junction with Tonle Sap, and dredging and other navigation improvements in the delta. Collectively, activities may include blasting of rocks and rapids, channel dredging to increase water depth, construction of locks and construction of upstream reservoirs for dry season water release.

Situated at the 'crossroads' between the Upper and Lower Mekong, and the Bassac and Tonle Sap Rivers, Chaktomuk junction in Phnom Penh is the key to flow distribution between the four river branches, and to their morphological and hydrological development. Changes in river flow have led to increased siltation at Chaktomuk junction over the years. There are concerns that this will result in potential blocking of the navigation channel to the port of Phnom Penh, so stabilization plans are under way to ensure that this essential shipping channel remains open.

Improvement of port facilities is also planned, through construction of new ports or upgrading existing ones. Port improvements may include shoreline development, measures that will increase vessel traffic, dredging and disposal of channel material.

Hydrologic regimes are subject to direct and indirect changes as a result of navigation improvements, dredging and other development activities in the basin. Undesirable results of changes to the hydrological regime include impairment of quality and quantity of the water supply, and ecological effects such as degradation of critical fish habitat.