Compression Ignition - CI or Diesel engines are currently considered the most fuel efficient combustion based drivetrain, and, for this reason, it has been historically used as the backbone for heavy duty markets, including transit bus fleets. At the same time, CI engines fueled by traditional crude oil based diesel fuel are facing the growing challenge of meeting the increasing stringent emission standards, specially on particulates matter, nitrogen oxides and greenhouse gases emissions limits. Moreover, petroleum based transport fuels are constantly faced by strategic and security concerns, due to the concentration of the main currently known reserves in political unstable regions. As such, it is both environmentally and economically important to find alternatives for crude oil based diesel fuel to be used in the transportation sector. Liquid biofuels can have attractive features like high energy density and potentially low air pollutant emissions, depending on their feedstock and processing methods. Ethanol potentially can contribute to replacing oil derived transportation fuels and reduce greenhouse gas emissions. Particularly important is the second-generation ethanol technology, produced from cellulosic biomass - with its intrinsic higher efficiency and lower costs - on the way to be commercially viable. Heavy duty engines can be ran basically with neat ethanol (with some technical modifications in the fuel and/or engines) as well as blended with additives (to maintain the blend stability and avoid phase separation). Ethanol has been used in transit bus fleets for more than 25 years on Sweden, in the city of Stockholm, to address the reduction of the high concentration of pollutants in the city center. More recently, ethanol heavy duty engines have also been evaluated in the so called “Bioethanol for Sustainable Transport” - BEST Program, to demonstrate the environmental benefits, engine technical/performance features and regulatory issues of ethanol as an alternative to fossil based urban transport fuels in some world cities, including São Paulo, the Brazilian city with the largest fleet of transit buses, which has been testing ethanol buses in revenue service with promising preliminary operational results, albeit with increased operational costs. This work is supposed to give an overview of ethanol use in heavy duty engines, with a focus on fuel properties and production methods, engine technology, performance, emissions and costs, as well as a snapshot on some of the current ethanol bus programs worldwide.