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VirtualBox is actually also a good example of the negative sides of relying on a cross platform toolkit: while it draws the widgets using native routines, the layout of the widget does not conform to the UI guidelines. Mac OS X specifies a certain distance that widgets are supposed to keep from window borders and other widgets. Qt or wxWidgets do not enforce these distances, nor do they enforce the default type faces or sizes.
By violating the layout guidelines, an application can draw using native widgets but still look alien to a Mac user.
Ok, there's been several comments mentioning Qt4 and WxWidgets (both of which I've used before but only very, very, very briefly in other projects). However, I need to know what the drawbacks are when compared to making one interface for each environment (KDE, Gnome, Unity, LXDE, etc). What do I gain by going that route instead of opting for a "one toolkit to rule them all"? What are the drawbacks on Qt4 vs WxWidgets?