Regulation - world political situation - world economic situation - disasters - wars - failure of major projects - and many more. All of that will affect the interest of investors and traders which in turn has an impact on demand and supply. Basically this is very general question, so I think you can get quite number of reasons if you do keyword search ^{[like your topic title].}

Next, you may ask what makes it worthless. But try to read further because basically bitcoin is a very volatile asset. Also it is relatively new currency and of course it is always possible to fail at some point such as technical failure and currency competition.