A number of bacterial toxins have sophisticated mechanisms for reaching their specific targets in mammalian cells, to exert their toxicity. This review focuses on the transport mechanisms of cholera toxin and botulinum neurotoxin complex. Cholera toxin is an ADP-ribosyltransferase toxin, and the covalent modification of heterotrimeric Gs protein in the cytosol leads to the activation of adenylyl cyclase and a sequence of events culminating in massive diarrheal disease. Here, we describe the structural features of this toxin and the transport pathway followed by this toxin from the plasma membrane to the cytosol of intestinal epithelial cells. Botulinum neurotoxin is a metalloprotease toxin that enters neurons, where it cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The food-borne botulism is manifested when the neurotoxin is absorbed from the digestive tract, enters the blood stream, and reaches the cytosol of the peripheral nerves. We overview the structural organization and the long journey followed by this toxin.