You will need a self-contained life support system involving plants and other renewable sources of food. You will need to build a spacecraft in orbit, because to build one on the ground would be too costly and wasteful of the resources needed to build a vehicle which will spend 99.99 percent of its time in space. You will need to solve many nasty biological issues related to how humans degenerate in space over long spans of time in 'zero-G'. You will need to devise a shielding system to protect the astronauts from exposure to solar flares.
These are just some of the things I can think of off hand.