Crucial issues
Most requirements for an autonomous colony on Mars can be fulfilled today, thanks to the experiences with manned orbital stations (ISS) and recent robot missions to the Red Planet. Also, there is advanced mining and recycling technology available. But there are some crucial issues to be clarified. Each of these issues can be a fundamental blocking point in the plan to make a colony independent from regular replenishments.
Energy
Energy is required mainly for food production and heating. The only available energy source seems to be solar power. Yet, the net energy gain under Martian environmental conditions for solar panels is unclear.
Money
The financial effort estimation reveals the enormous costs for the transport to the Red Planet. Establishing a whole colony requires many shipments. Both private fund raising and government programs are based upon a broad public interest. Enough people must be convinced to support the enterprise.