One route to reducing global CO2 emissions is to improve the energy efficiency of machines. Even small improvements in efficiency can be valuable, especially in cases where an efficiency improvement can be realized over many millions of newly produced machines. For example, conventional passenger car combustion engines are being downsized (and also downspeeded). Increasingly, they are running on lower-viscosity engine lubricants (such as SAE 0W-20 or lower viscosity grades) and often also have stop–start systems fitted (to prevent engine idling when the vehicle is stopped). Some of these changes result in higher levels of mixed and boundary friction, and so accurate estimation of mixed/boundary friction losses is becoming of increased importance, for both estimating friction losses and wear volumes. Traditional approaches to estimating mixed/boundary friction, which employ real area of contact modelling, and assumptions such as the elastic deformation of asperities, are widely used, but recent experimental data suggest that some of these approaches underestimate mixed/boundary friction losses. In this paper, a discussion of the issues involved in reliably estimating mixed/boundary friction losses in machine elements is undertaken, highlighting where the key uncertainties lie. Mixed/boundary lubrication losses in passenger car and heavy-duty internal combustion engines are then estimated and compared with published data, and a detailed description of how friction is related to fuel consumption in these vehicles, on standard fuel economy driving cycles, is given. Knowing the amount of fuel needed to overcome mixed/boundary friction in these vehicles enables reliable estimates to be made of both the financial costs of mixed/boundary lubrication for today’s vehicles and their associated CO2 emissions, and annual estimates are reported to be approximately USD 290 billion with CO2 emissions of 480 million tonnes.