With all of the problems that could go wrong in space, nothing is more serious, more threatening towards human settlement in the cosmos than humans themselves.
Despite intense training physically and mentally, long term isolation may be more than most humans can bare, with irritation, boredom or the “need to breed” causing unnecessary conflict to arise. Usually frequent contact with ones family, alongside of random gifts are enough to keep a person in check mentally, but it may be unreasonable to expect someone to remain sane while separated from kin for years.
One way to resolve this issue would be to enlist families of future colonists to travel alongside their loved ones in order to not only reduce stress, but also help settle foreign worlds. Despite the fact that raising a families millions of miles away from Earth may sound risky (especially if parents have young children), the experience may serve to inform our race whether or not we will be able to call hostile worlds our own.
Some organizations seem to have envisioned colonists raising their families off world, most notably on the red planet. 4Frontiers, a company dedicated towards colonizing the Moon, Mars and eventually the asteroids themselves seems to have envisioned this concept which they frequently portray in their stories of kids growing up on the Martian landscape.
Raising a family off world may prove to be more difficult than on Earth, with the hazards of space, technology and supplies being major hurdles to overcome. But families seem to have a stronger group bond than strangers which may enable humanity to overcome many of the problems of isolation, enabling us to call distant worlds like Mars our own.