Santa Cruz is Bolivia’s main transportation hub. You can fly in and out of Santa Cruz directly from Miami, Mexico, Sao Paulo, Rio de Janeiro, Buenos Aires, Panama, Caracas, Bogota, Lima, Cuzco, Asuncion, Montevideo, Manaos, Cordoba, Jujuy, Salta, Arica, Santiago and La Paz. By train from Argentina and Brazil.
In the city, while in the Centro you can walk everywhere, from neighborhood to neighborhood by taxi (they won’t cost you more then US$ 2).
In the countryside you may want to take buses to Samaipata and Buena Vista (Amboro National Park). For the Jesuit missions you can take a bus or fly.
I highly recommend renting a car if you are going to the country side (preferably an all terrain 4x4). There are several car rental in Santa Cruz and you only need and international drivers license.
Bus companies: Bolivar offers a good ride, but bus windows do not close completely making for a drafty ride at night. Also, they promise they will make stops for food, etc. but they do not always make the stops they promise.
From the USA you can fly to Santa Cruz with either American Airlines, Continental and LAB Bolivian Airlines, there are 4 daily flight between Santa Cruz and Miami and 4 flights a week between Santa Cruz and Houston.
From neighboring countries (Peru, Brazil, Argentina, Paraguay and Chile), there are direct fights from all major cities of the neighboring countries and Santa Cruz.
From Santa Cruz you can flight to any city or major town in Bolivia. Santa Cruz is the countries main airport.
If you are already in Bolivia and can’t afford to fly you can travel to Santa Cruz by bus, or by train from Brazil and Argentina.
In Santa Cruz the best way to get from neighborhood to neighborhood is by taxi, they are usually very cheap, and if you stay in a hotel you can get a list of “Radiomoviles” which are on call taxis which are very save as well.
In the downtown area or in Equipetrol just walk.
To get to the country side you can rent a car (preferably a 4x4 if you want to go to more exciting places and be in contact with nature), or take a bus or bike.