The main risk for business travellers in Medellin is from petty crime. Opportunistic street crime, including pickpocketing and muggings, as well as car theft and burglaries, occurs throughout the city. Most violent crime is concentrated in the underdeveloped areas on the north-eastern and north-western outskirts of the city, known locally as 'comunas'. However, petty crime can also occur in the main business and tourist areas. Business travellers should observe basic security precautions and avoid venturing outside the main business and tourist centres unless accompanied by a trusted local guide. Basic security precautions are necessary at all times, such as always carrying a small amount of money in an easily accessible place that can be handed over immediately to a mugger.

The city has a compact, modern centre where most business is located. Roads are divided into those crossing the city east and west (calles) parallel to the Medellin River, and those bisecting it north and south (carreras). Larger roads are known as avenidas or autopistas. In the centre, many streets still bear their proper names as well as their numerical designation. The city's upmarket areas are Las Palmas and the southern suburb of El Poblado.